Abstract

Previous studies of Aβ plasma as a biomarker for Alzheimer's disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ(1-40) and Aβ(1-42) plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ(1-42) measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ(1-42) showed mild correlation with other biomarkers of Aβ pathology and were associated with infarctions in MRI. Longitudinal measurements of Aβ(1-40) and Aβ(1-42) plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of Aβ pathology (PIB, CSF and plasma Aβ) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma Aβ measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma Aβ measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma Aβ as well as the need for longer term studies to determine the clinical utility of measuring plasma Aβ.

Amyloid beta (Aβ) 1–42 levels in the different cognitive groups stratified by CSF signature and age. Aβ1–42 levels in cognitively normal (CN) stable, mild cognitive impairment (MCI) stable and progressors and Alzheimer’s disease (AD) subjects, stratified by normal and pathological cerebrospinal fluid signature (CSF). There was an interaction between age and diagnostic group in the three groups with pathological CSF signature: MCI stables (p < 0.001), MCI progressors (p = 0.021) and AD (p = 0.034). Only the groups with younger subjects and pathological CSF had a difference in Aβ1–42 levels than the pooled cognitively normals with normal CSF signature

Amyloid beta (Aβ) plasma biomarker changes along time in cognitive normal subjects with normal cerebrospinal fluid (CSF), mild cognitive impairment stable and progressor subjects with pathological CSF and Alzheimer’s disease (AD) subjects with pathological CSF with 95% CI based on SE. All the models were adjusted for age and took into consideration the interaction between age and diagnostic category. a Aβ1–42 along time: There is an increase in the concentration across time (p <0.001), except in AD cases (p = 0.067), and mild cognitive impairment (MCI) progressors have lower levels than MCI stables and cognitive normals (CN) (p = 0.039). b Aβ1–40 along time: There is an increase in the concentration across time (p < 0.001), except in AD cases (p = 0.372), and no difference between diagnostic groups (p = 0.213). c AβR along time: There was a decrease of the ratio across time (p = 0.042) except in AD cases (p = 0.902), but no difference between diagnostic groups (p = 1.0). Aβ amyloid beta